Melanin concentrating hormone (MCH) is a 19 amino acid neuropeptide produced in the lateral hypothalamic area and zona incerta. Extensive evidence supports the orexigenic activity of MCH. MCHR1−/− mice have been reported to be lean and hyper metabolic, indicating that the R1 isoform mediates at least some of the metabolic effects of MCH.
PCT International publication WO 03/033476 A1 discloses pyrimidinones as melanin concentrating hormone receptor antagonists. PCT international publications WO2005/047293 A1 discloses compounds said to be useful as MCH antagonists. Dyck, B et al (Journal of Medicinal Chemistry (2006) 49(13) 3753-3756) entitled “A Thienopyridazinone-Based Melanin-Concentrating Hormone Receptor 1 Antagonist with Potent In Vivo Anorectic Properties” discloses thienopyridazinone compounds said to be useful as MCH antagonists.
There is a need for potent, selective and therapeutically effective agents to better control dietary habits, minimize the preponderance of obesity, treat, and/or ameliorate the effects of obesity and Related Diseases. The present invention provides particularly preferred compounds having high potency, selectivity and/or in-vivo efficacy as MCH antagonists useful for the treatment of obesity and related diseases.